Reduced meal frequency alleviates high-fat diet-induced lipid accumulation and inflammation in adipose tissue of pigs under the circumstance of fixed feed allowance

Abstract

Purpose

The present study was conducted to determine whether reduced meal frequency (MF) could restore high-fat diet (HFD)-modified phenotypes and microbiota under the condition of fixed feed allowance.

Methods

A total of 32 barrows with initial weight of 61.6 ± 0.8 kg were assigned to two diets [control diet (CON) versus HFD] and two meal frequencies [12 equal meals/day (M12) versus 2 equal meals/day (M2)], the trial lasted 8 weeks. The lipid metabolism and inflammatory response in adipose tissue as well as the profiles of intestinal microbiota and bacterial-derived metabolites were determined.

Results

M2 versus M12 feeding regimen decreased perirenal fat weight and serum triglyceride and liposaccharide (LPS) concentrations in HFD-fed pigs (P < 0.05). Reduced MF down-regulated mRNA expression of lipoprotein lipase, CD36 molecule, interleukin 1 beta, tumor necrosis factor alpha, toll-like receptor 4, myeloid differentiation factor 88 (MYD88), and nuclear factor kappa beta 1 as well as protein expression of MYD88 in perirenal fat of HFD-fed pigs (P < 0.05). M2 feeding regimen increased abundance of Prevotella and decreased abundance of Bacteroides in colonic content of HFD-fed pigs (P < 0.05). No difference in short-chain fatty acids (SCFAs) profile in colonic content was observed among four groups (P > 0.05).

Conclusion

Our results suggested that M2 versus M12 feeding regimen ameliorated HFD-induced fat deposition and inflammatory response by decreasing fatty acid uptake and deactivating LPS/TLR4 signaling pathway in adipose tissue and restoring microbiota composition in distal intestine, without affecting SCFAs profile in distal luminal content.

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References

  1. 1.

    Cani PD, Rodrigo B, Knauf C et al (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. https://doi.org/10.2337/db07-1403

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Johnson L, Mander AP, Jones LR et al (2008) Energy-dense, low-fiber, high-fat dietary pattern is associated with increased fatness in childhood. Am J Clin Nutr 87(4):846–854

    CAS  Article  Google Scholar 

  3. 3.

    Leidy HJ, Armstrong CLH, Tang M et al (2010) The influence of higher protein intake and greater eating frequency on appetite control in overweight and obese men. Obesity 18(9):1725–1732

    CAS  Article  Google Scholar 

  4. 4.

    Schwarz NA, Rigby BR, La Bounty P et al (2011) A review of weight control strategies and their effects on the regulation of hormonal balance. J Nutr Metab. https://doi.org/10.1155/2011/237932

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Edelstein SL, Barrett-Connor EL, Wingard DL et al (1992) Increased MF associated with decreased cholesterol concentrations; Rancho Bernardo, CA, 1984–1987. Am J Clin Nutr 55(3):664–669

    CAS  Article  Google Scholar 

  6. 6.

    Palmer MA, Capra S, Baines SK (2009) Association between eating frequency, weight, and health. Nutr Rev 67(7):379–390

    Article  Google Scholar 

  7. 7.

    Forslund HB, Lindroos AK, Sjöström L et al (2002) Meal patterns and obesity in Swedish women-a simple instrument describing usual meal types, frequency and temporal distribution. Eur J Clin Nutr 56(8):740

    Article  Google Scholar 

  8. 8.

    Koopman KE, Caan MWA, Nederveen AJ et al (2014) Hypercaloric diets with increased MF, rather than meal size, increase intrahepatic triglycerides: a randomized controlled trial. Hepatology 60(2):545–553

    CAS  Article  Google Scholar 

  9. 9.

    Liu J, Liu Z, Chen L et al (2016) iTRAQ-based proteomic analysis reveals alterations in the liver induced by restricted MF in a pig model. Nutrition 32(7–8):871–876

    CAS  Article  Google Scholar 

  10. 10.

    Bäckhed F, Manchester JK, Semenkovich CF et al (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci 104(3):979–984

    Article  Google Scholar 

  11. 11.

    Duca FA, Sakar Y, Lepage P et al (2014) Replication of obesity and associated signaling pathways through transfer of microbiota from obese prone rat. Diabetes. https://doi.org/10.2337/db13-1526

    Article  PubMed  Google Scholar 

  12. 12.

    Kim KA, Gu W, Lee IA et al (2012) High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One 7(10):e47713

    CAS  Article  Google Scholar 

  13. 13.

    Perry RJ, Peng L, Barry NA et al (2016) Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome. Nature 534(7606):213

    CAS  Article  Google Scholar 

  14. 14.

    Xiao L, Estellé J, Kiilerich P et al (2016) A reference gene catalogue of the pig gut microbiome. Nat Microbiol 1:16161

    CAS  Article  Google Scholar 

  15. 15.

    Liu JB, Yan HL, Cao SC et al (2018) Effect of feed intake level on the determination of apparent and standardized total tract digestibility of phosphorus for growing pigs. Anim Feed Sci Technol 246:137–143

    CAS  Article  Google Scholar 

  16. 16.

    Bazin R, Ferré P (2001) Assays of lipogenic enzymes. Methods Mol Biol 155:121–127

    CAS  PubMed  Google Scholar 

  17. 17.

    Peng S, Shi Z, Gao Q et al (2017) Dietary n-3 LC-PUFAs affect lipoprotein lipase (LPL) and fatty acid synthase (FAS) activities and mRNA expression during vitellogenesis and ovarian fatty acid composition of female silver pomfret (Pampus argenteus) broodstock. Aquacult Nutr 23(4):692–701

    CAS  Article  Google Scholar 

  18. 18.

    Liu J, Cao S, Liu M et al (2018) A high nutrient dense diet alters hypothalamic gene expressions to influence energy intake in pigs born with low birth weight. Sci Rep 8(1):5514

    Article  Google Scholar 

  19. 19.

    Bergström A, Licht TR, Wilcks A et al (2012) Introducing GUt Low-Density Array (GULDA)—a validated approach for qPCR-based intestinal microbial community analysis. FEMS Microbiol Lett 337(1):38–47

    Article  Google Scholar 

  20. 20.

    Hatori M, Vollmers C, Zarrinpar A et al (2012) Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab 15:848–860

    CAS  Article  Google Scholar 

  21. 21.

    Kim KH, Kim YH, Son JE et al (2017) Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage. Cell Res 27(11):1309–1326

    CAS  Article  Google Scholar 

  22. 22.

    Li G, Xie C, Lu S et al (2017) Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota. Cell Metab 26(4):672–685

    CAS  Article  Google Scholar 

  23. 23.

    Patterson RE, Sears DD (2017) Metabolic Effects of Intermittent Fasting. Annu Rev Nutr 37:371–393

    CAS  Article  Google Scholar 

  24. 24.

    Yan H, Zheng P, Yu B et al (2017) Postnatal high-fat diet enhances ectopic fat deposition in pigs with intrauterine growth retardation. Eur J Nutr 56(2):483–490

    CAS  Article  Google Scholar 

  25. 25.

    Zhao H, Li K, Tang JY et al (2015) Expression of selenoprotein genes is affected by obesity of pigs fed a high-fat diet. J Nutr 145(7):1394–1401

    CAS  Article  Google Scholar 

  26. 26.

    Hatting M, Rines AK, Luo C et al (2017) Adipose tissue CLK2 promotes energy expenditure during high-fat diet intermittent fasting. Cell Metab 25(2):428–437

    CAS  Article  Google Scholar 

  27. 27.

    Chaix A, Zarrinpar A, Miu P et al (2014) Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab 20(6):991–1005

    CAS  Article  Google Scholar 

  28. 28.

    Chaix A, Lin T, Le HD et al (2018) Time-restricted feeding prevents obesity and metabolic syndrome in mice lacking a circadian clock. Cell Metab. https://doi.org/10.1016/j.cmet.2018.08.004

    Article  PubMed  Google Scholar 

  29. 29.

    Kotas ME, Medzhitov R (2015) Homeostasis, inflammation, and disease susceptibility. Cell 160(5):816–827

    CAS  Article  Google Scholar 

  30. 30.

    Vaure C, Liu Y (2014) A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front Immunol 5:316

    Article  Google Scholar 

  31. 31.

    O’Neill LA, Golenbock D, Bowie AG (2013) The history of Toll-like receptors—redefining innate immunity. Nat Rev Immunol 13(6):453–460

    Article  Google Scholar 

  32. 32.

    Liu J, He J, Yang Y et al (2014) Effects of intrauterine growth retardation and postnatal high-fat diet on hepatic inflammatory response in pigs. Arch Anim Nutr 68(2):111–125

    CAS  Article  Google Scholar 

  33. 33.

    Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci 104:979–984

    Article  Google Scholar 

  34. 34.

    Bäckhed F, Ding H, Wang T et al (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci 101:15718–15723

    Article  Google Scholar 

  35. 35.

    Duncan SH, Lobley G, Holtrop G et al (2008) Human colonic microbiota associated with diet, obesity and weight loss. Int J Obesity 32(11):1720–1724

    CAS  Article  Google Scholar 

  36. 36.

    Wu GD, Chen J, Hoffmann C et al (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334(6052):105–108

    CAS  Article  Google Scholar 

  37. 37.

    Zarrinpar A, Chaix A, Yooseph S et al (2014) Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell Metab 20(6):1006–1017

    CAS  Article  Google Scholar 

  38. 38.

    Kim KA, Jeong JJ, Yoo SY et al (2016) Gut microbiota lipopolysaccharide accelerates inflamm-aging in mice. BMC Microbiol 16(1):9

    Article  Google Scholar 

  39. 39.

    Löwer M, Schneider G (2009) Prediction of type III secretion signals in genomes of gram-negative bacteria. PLoS One 4(6):e5917

    Article  Google Scholar 

  40. 40.

    Schwiertz A, Taras D, Schäfer K et al (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity 18(1):190–195

    Article  Google Scholar 

  41. 41.

    Den BG, Bleeker A, Gerding A et al (2015) Short-chain fatty acids protect against high-fat diet–induced obesity via a PPARγ-dependent switch from lipogenesis to fat oxidation. Diabetes 64(7):2398–2408

    Article  Google Scholar 

  42. 42.

    Koh A, De Vadder F, Kovatcheva-Datchary P et al (2016) From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165(6):1332–1345

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This study was supported by the National Natural Science Foundation of China (31802069) and Sichuan Science and Technology Program (2018JY0225).

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Correspondence to Jingbo Liu.

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Fig. S1

Effects of diet type and meal frequency on mRNA abundances of short-chain fatty acids receptors in perirenal fat of finishing pigs. (a) FFAR2, free fatty acid receptor 2, also known as GPR43; (b) FFAR3, free fatty acid receptor 3, also known as GPR41. CON, control diet; HF, high-fat diet; M12, pigs receiving 12 equal meals per day; M2, pigs receiving 2 equal meals per day, MF, meal frequency, NS, no significant difference. Means with different lowercase letters represent significant differences between groups (PDF 494 KB)

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Yan, H., Cao, S., Li, Y. et al. Reduced meal frequency alleviates high-fat diet-induced lipid accumulation and inflammation in adipose tissue of pigs under the circumstance of fixed feed allowance. Eur J Nutr 59, 595–608 (2020). https://doi.org/10.1007/s00394-019-01928-3

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Keywords

  • Meal frequency
  • High-fat diet
  • Lipid metabolism
  • Inflammation
  • Microbiota
  • Short-chain fatty acids